Biology Reference
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Fig. 9.
Retrieving PIM by fragment-based virtual lead design. (a) Map of most
favorable phenyl poses in IDO active site. (b) Map of most favorable imidazole poses.
(c) Map of second most favorable phenyl pose and most favorable imidazole pose.
(d) Superposition of (c) with the PIM X-ray structure (in orange).
rate of more than 60% clearly demonstrates the efficiency of the frag-
ment-based virtual lead design approach. All active substances represent
straightforward organic frameworks of low molecular weight with many
purchasable or easily synthesizable derivatives.
An example of a successful ligand design by this fragment-based
approach is given in Fig. 10. The quinoline framework has been linked
with a hydroxy and an amine side chain, thereby yielding the commer-
cially available compound 5-amino-8-hydroxyquinoline. Subsequent
testing in the enzymatic assay confirmed its activity as an IDO inhibitor
